The Na+/K+-ATPase and the amyloid-beta peptide aβ1-40 control the cellular distribution, abundance and activity of TRPC6 channels

Sylvain Chauvet, Marielle Boonen, Mireille Chevallet, Louis Jarvis, Addis Abebe, Mohamed Benharouga, Peter Faller, Michel Jadot, Alexandre Bouron

Résultats de recherche: Contribution à un journal/une revueArticle

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The Na(+)/K(+)-ATPase interacts with the non-selective cation channels TRPC6 but the functional consequences of this association are unknown. Experiments performed with HEK cells over-expressing TRPC6 channels showed that inhibiting the activity of the Na(+)/K(+)-ATPase with ouabain reduced the amount of TRPC6 proteins and depressed Ca(2+) entry through TRPC6. This effect, not mimicked by membrane depolarization with KCl, was abolished by sucrose and bafilomycin-A, and was partially sensitive to the intracellular Ca(2+) chelator BAPTA/AM. Biotinylation and subcellular fractionation experiments showed that ouabain caused a multifaceted redistribution of TRPC6 to the plasma membrane and to an endo/lysosomal compartment where they were degraded. The amyloid beta peptide Aβ1-40, another inhibitor of the Na(+)/K(+)-ATPase, but not the shorter peptide Aβ1-16, reduced TRPC6 protein levels and depressed TRPC6-mediated responses. In cortical neurons from embryonic mice, ouabain, veratridine (an opener of voltage-gated Na(+) channel), and Aβ1-40 reduced TRPC6-mediated Ca(2+) responses whereas Aβ1-16 was ineffective. Furthermore, when Aβ1-40 was co-added together with zinc acetate it could no longer control TRPC6 activity. Altogether, this work shows the existence of a functional coupling between the Na(+)/K(+)-ATPase and TRPC6. It also suggests that the abundance, distribution and activity of TRPC6 can be regulated by cardiotonic steroids like ouabain and the naturally occurring peptide Aβ1-40 which underlines the pathophysiological significance of these processes.

langue originaleAnglais
Numéro d'article17657
Pages (de - à)2957-2965
Nombre de pages9
journalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Numéro de publication11
Les DOIs
étatPublié - 1 nov. 2015

Empreinte digitale

Amyloid beta-Peptides
Ouabain
Zinc Acetate
Veratridine
Biotinylation
Cardiac Glycosides
Peptides
Chelating Agents
Sucrose
Cations
Proteins
Cell Membrane
Neurons
Membranes
sodium-translocating ATPase

Citer ceci

Chauvet, Sylvain ; Boonen, Marielle ; Chevallet, Mireille ; Jarvis, Louis ; Abebe, Addis ; Benharouga, Mohamed ; Faller, Peter ; Jadot, Michel ; Bouron, Alexandre. / The Na+/K+-ATPase and the amyloid-beta peptide aβ1-40 control the cellular distribution, abundance and activity of TRPC6 channels. Dans: Biochimica et Biophysica Acta - Molecular Cell Research. 2015 ; Vol 1853, Numéro 11. p. 2957-2965.
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abstract = "The Na(+)/K(+)-ATPase interacts with the non-selective cation channels TRPC6 but the functional consequences of this association are unknown. Experiments performed with HEK cells over-expressing TRPC6 channels showed that inhibiting the activity of the Na(+)/K(+)-ATPase with ouabain reduced the amount of TRPC6 proteins and depressed Ca(2+) entry through TRPC6. This effect, not mimicked by membrane depolarization with KCl, was abolished by sucrose and bafilomycin-A, and was partially sensitive to the intracellular Ca(2+) chelator BAPTA/AM. Biotinylation and subcellular fractionation experiments showed that ouabain caused a multifaceted redistribution of TRPC6 to the plasma membrane and to an endo/lysosomal compartment where they were degraded. The amyloid beta peptide Aβ1-40, another inhibitor of the Na(+)/K(+)-ATPase, but not the shorter peptide Aβ1-16, reduced TRPC6 protein levels and depressed TRPC6-mediated responses. In cortical neurons from embryonic mice, ouabain, veratridine (an opener of voltage-gated Na(+) channel), and Aβ1-40 reduced TRPC6-mediated Ca(2+) responses whereas Aβ1-16 was ineffective. Furthermore, when Aβ1-40 was co-added together with zinc acetate it could no longer control TRPC6 activity. Altogether, this work shows the existence of a functional coupling between the Na(+)/K(+)-ATPase and TRPC6. It also suggests that the abundance, distribution and activity of TRPC6 can be regulated by cardiotonic steroids like ouabain and the naturally occurring peptide Aβ1-40 which underlines the pathophysiological significance of these processes.",
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The Na+/K+-ATPase and the amyloid-beta peptide aβ1-40 control the cellular distribution, abundance and activity of TRPC6 channels. / Chauvet, Sylvain; Boonen, Marielle; Chevallet, Mireille; Jarvis, Louis; Abebe, Addis; Benharouga, Mohamed; Faller, Peter; Jadot, Michel; Bouron, Alexandre.

Dans: Biochimica et Biophysica Acta - Molecular Cell Research, Vol 1853, Numéro 11, 17657, 01.11.2015, p. 2957-2965.

Résultats de recherche: Contribution à un journal/une revueArticle

TY - JOUR

T1 - The Na+/K+-ATPase and the amyloid-beta peptide aβ1-40 control the cellular distribution, abundance and activity of TRPC6 channels

AU - Chauvet, Sylvain

AU - Boonen, Marielle

AU - Chevallet, Mireille

AU - Jarvis, Louis

AU - Abebe, Addis

AU - Benharouga, Mohamed

AU - Faller, Peter

AU - Jadot, Michel

AU - Bouron, Alexandre

N1 - Copyright © 2015. Published by Elsevier B.V.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - The Na(+)/K(+)-ATPase interacts with the non-selective cation channels TRPC6 but the functional consequences of this association are unknown. Experiments performed with HEK cells over-expressing TRPC6 channels showed that inhibiting the activity of the Na(+)/K(+)-ATPase with ouabain reduced the amount of TRPC6 proteins and depressed Ca(2+) entry through TRPC6. This effect, not mimicked by membrane depolarization with KCl, was abolished by sucrose and bafilomycin-A, and was partially sensitive to the intracellular Ca(2+) chelator BAPTA/AM. Biotinylation and subcellular fractionation experiments showed that ouabain caused a multifaceted redistribution of TRPC6 to the plasma membrane and to an endo/lysosomal compartment where they were degraded. The amyloid beta peptide Aβ1-40, another inhibitor of the Na(+)/K(+)-ATPase, but not the shorter peptide Aβ1-16, reduced TRPC6 protein levels and depressed TRPC6-mediated responses. In cortical neurons from embryonic mice, ouabain, veratridine (an opener of voltage-gated Na(+) channel), and Aβ1-40 reduced TRPC6-mediated Ca(2+) responses whereas Aβ1-16 was ineffective. Furthermore, when Aβ1-40 was co-added together with zinc acetate it could no longer control TRPC6 activity. Altogether, this work shows the existence of a functional coupling between the Na(+)/K(+)-ATPase and TRPC6. It also suggests that the abundance, distribution and activity of TRPC6 can be regulated by cardiotonic steroids like ouabain and the naturally occurring peptide Aβ1-40 which underlines the pathophysiological significance of these processes.

AB - The Na(+)/K(+)-ATPase interacts with the non-selective cation channels TRPC6 but the functional consequences of this association are unknown. Experiments performed with HEK cells over-expressing TRPC6 channels showed that inhibiting the activity of the Na(+)/K(+)-ATPase with ouabain reduced the amount of TRPC6 proteins and depressed Ca(2+) entry through TRPC6. This effect, not mimicked by membrane depolarization with KCl, was abolished by sucrose and bafilomycin-A, and was partially sensitive to the intracellular Ca(2+) chelator BAPTA/AM. Biotinylation and subcellular fractionation experiments showed that ouabain caused a multifaceted redistribution of TRPC6 to the plasma membrane and to an endo/lysosomal compartment where they were degraded. The amyloid beta peptide Aβ1-40, another inhibitor of the Na(+)/K(+)-ATPase, but not the shorter peptide Aβ1-16, reduced TRPC6 protein levels and depressed TRPC6-mediated responses. In cortical neurons from embryonic mice, ouabain, veratridine (an opener of voltage-gated Na(+) channel), and Aβ1-40 reduced TRPC6-mediated Ca(2+) responses whereas Aβ1-16 was ineffective. Furthermore, when Aβ1-40 was co-added together with zinc acetate it could no longer control TRPC6 activity. Altogether, this work shows the existence of a functional coupling between the Na(+)/K(+)-ATPase and TRPC6. It also suggests that the abundance, distribution and activity of TRPC6 can be regulated by cardiotonic steroids like ouabain and the naturally occurring peptide Aβ1-40 which underlines the pathophysiological significance of these processes.

KW - Aβ peptides

KW - Lysosomes

KW - Na/K pump

KW - Neurons

KW - Trafficking

KW - TRPC6

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U2 - 10.1016/j.bbamcr.2015.09.004

DO - 10.1016/j.bbamcr.2015.09.004

M3 - Article

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VL - 1853

SP - 2957

EP - 2965

JO - Biochimica et Biophysica Acta - Molecular Cell Research

JF - Biochimica et Biophysica Acta - Molecular Cell Research

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M1 - 17657

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